The FDA recently approved a new drug known as Adulhelm, or aducanumab, to treat Alzheimer’s disease. The first new treatment for the condition since 2003, some of the scientific community doubt its effectiveness.
The specific causes of Alzheimer’s are unknown. However, the condition has been linked to the formation of amyloid-beta plaques in the brain that lead to a loss of neurons and their connections. These changes are thought to adversely affect a person's cognitive abilities.
Prior approval, researchers evaluated the drug’s effectiveness in three separate studies including 3,482 patients. In the end, the studies found that patients who received the treatment had significant dose-and time-dependent reductions in amyloid-beta plaques, while patients in control groups did not see any reduction in amyloid-beta plaques.
Given that these plaques are thought to have cognitive effects, the drug was approved on the basis that reducing these plaques could improve clinical outcomes. But this is where the controversy lies. While anti-amyloid antibodies, such as Pfizer’s bapineuzumab, have been shown to reduce amyloid-beta plaques in the brain, they have not been accompanied with a meaningful impact on clinical outcomes. Like this drug, while Adulhelm seems to purge the brain of detectable fibrillar amyloid, it does not seem to provide consistent meaningful benefit for patients.
“The FDA’s opinion that amyloid reduction should lead to meaningful clinical benefit, an opinion shared by many dementia researchers, flies in the face of a decade of failures with bapineuzumab, solanezumab, and others.” writes founding and current director of the Mount Sinai Center for Cognitive Health and NFL Neurological Care, Samuel E Gandy, MD, PhD, for STAT news.
“It is possible that personal polygenic risk scores might point to individuals in whom some early initiation of amyloid reduction might yield meaningful benefit, but that science is not yet in hand. Moreover, current data suggest that this early age of initiation of amyloid reduction might be the third or fourth decade of life, far earlier than the Aduhelm approval anticipates.”
Further controversies around the drug include one of its two Phase 3 trials having uninterpretable results as the control group failed to decline as quickly as expected. The researchers also did not measure levels of neurofilament light chain (NfL) among patients, a biomarker for cognitive decline. The high cost of the drug, at $56,000 per year (discluding yearly physician costs, infusion center and imaging costs) is also prohibitive to most.